Orexins are neuropeptides that are involved in the regulation of the sleep-wake cycle and play an important role in maintaining human awake. Suvorexant is an Orexins receptor antagonist and improves the sleep of patients by blocking the transmission of messages by Orexins. The US Food and Drug Administration (FDA) approved the launch of Merck's new insomnia drug suvorexant (Trade name: Belsomra) on Aug. 13, 2014.
The synthetic route of this compound is reported in the following documents.
(1) The synthetic route reported in US2008/132490 is as follows.
(2) The synthetic route reported in Org. Process Res. Dev. 2011, 15, 367-375 is as follows.
(3) The synthetic route reported in WO2012148553 and J. Am. Chem. Soc. 2011, 133, 8362-8371 is as follows.

The above three routes have the following disadvantages: a highly toxic compound, methyl vinyl ketone, is used as a starting material, which is highly irritating to eyes, skin, mucous and upper respiratory tract, and is difficult to handle during use; in the preparation process of route (1), chiral column is required for resolution, which is not suitable for industrial large-scale production, and the overall yield of the route is low; the process in route (2) requires the use of chiral resolving reagents, and results in a low yield, a huge waste of material and increased cost; heavy metal ruthenium is used in route (3) to catalyze asymmetric reductive amination, which is costly and environmentally unfriendly.
(4) WO2015008218 reported the specific use of N-Boc N′-benzylethylenediamine as a raw material to prepare suvorexant.
Reagents such as 1,8-diazabicyclo (5.4.0) undec-7-ene (DBU), ketene, cyanuric chloride, Cu(OAc)2 and the like were used in the preparation process of this route. Additionally, (+) 2,3-dibenzoyl-D-tartaric acid was used for resolution, and the resulted ee value is not disclosed. The whole process has a long route, and the operation for reaction is cumbersome. The atomic utilization rate may not be high by using the general resolving agent not for kinetic resolution. These result in an increased cost of the route, which is not conducive to commercial production.
The specific reaction formula is as follows:

It can be seen that the development of new methods for synthesizing suvorexant and its intermediate compounds to overcome the shortcomings of the prior art is of great significance.